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Background: Admission to the intensive care unit (ICU) is frequently required for patients with acute leukemia (AL) because of life-threatening complications such as intracranial hemorrhage (IH). In this study, we evaluated the impact of IH on survival and neurological outcomes in this population. Methods: This was a single-center retrospective cohort study including adult patients with AL requiring ICU admission and experiencing IH between 2002 and 2019 at Saint Louis Hospital. Leukemia type was determined according to the French–American–British classification. Brain imaging (either computed tomography or magnetic resonance imaging) was available for all the patients. The primary endpoint of the study was to describe the clinical and biological characteristics and evaluate the mortality and neurological outcome of patients hospitalized in the ICU with newly diagnosed AL and IH. The secondary endpoint was to identify predictive factors of IH in these patients. Results: Thirty-five patients with AL were included, median age of the patients was 59.00 (interquartile range [IQR]: 36.00–66.00) years. Twenty-nine patients (82.9%) had acute myeloid leukemia, including 12 patients with acute promyelocytic leukemia. Thrombocytopenia was constant, and 48.5% of patients had disseminated intravascular coagulation (DIC). At ICU admission, the median Sequential Organ Failure Assessment score was 5 (IQR: 3–9). The median time between AL onset and IH was 2.0 (IQR: 0.0–9.5) days. The ICU and hospital mortality rates were 60.0% (n =21) and 65.7% (n=23), respectively. In univariate analysis, mechanical ventilation and stupor were associated with mortality, but DIC and acute promyelocytic leukemia were not. Upon multivariate analysis, stupor or coma was the only factor significantly associated with a poor outcome (odds ratio = 8.56, 95 % confidence interval: 2.40 to 30.46). Conclusion: IH is associated with a high mortality rate in AL patients, with stupor or coma at the onset of intracranial bleeding being independently associated with poor outcomes.

CD19-specific chimeric antigen receptor T (CAR-T) cell therapy has recently been shown to improve the prognosis of refractory diffuse large B-cell lymphoma (DLBCL). However, CAR-T cells may induce numerous adverse events, in particular cytokine release syndrome (CRS) which is frequently associated with cardiovascular manifestations. Among the latter, acute pericardial effusion represents less than 1% of cases and cardiac tamponade has only been reported once. The management and outcome of these severe complications are not well established. We report here, a case of cardiac tamponade associated with CRS in a context of CAR-T cell therapy, which required urgent pericardiocentesis.Case summaryA 65-year-old man with refractory DLBCL was treated with CAR-T cell therapy. He had a history of dilated cardiomyopathy with preserved ejection fraction and transient atrial fibrillation. A pericardial localization of the lymphoma was observed on the second relapse. One day after CAR-T cell infusion the patient was diagnosed with grade 1 CRS. Due to hypotension, he was treated with tocilizumab and dexamethasone, and then transferred to intensive care unit (ICU). Echocardiography performed at ICU admission showed acute pericardial effusion with signs of right ventricular heart failure due to cardiac tamponade. It was decided to perform pericardiocentesis despite grade IV thrombocytopenia in a context of aplasia. Analysis of pericardial fluid showed a large number of lymphoma cells and 73% of CAR-T cells amongst lymphocytes, a level that was similar in blood. Hemodynamic status improved after pericardiocentesis, and no recurrence of pericardial effusion was observed. The presence of a high count of activated CAR-T cells in the pericardial fluid as well as the short interval between CAR-T cells injection and the symptoms appear as potential arguments for a direct action of CAR-T cells in the mechanism of this adverse event. The patient was discharged from ICU after two days and initially exhibited a good response to DLBCL treatment. Unfortunately, he died fifty days after starting CAR-T cell therapy due to a new DLBCL relapse.ConclusionPatients with a pericardial localization of DLBCL should be assessed for a risk of cardiac tamponade if receiving CAR-T cell therapy and presenting CRS. In this case, cardiac tamponade seems directly related to CAR-T cell expansion. Pericardiocentesis should be considered as a feasible and effective treatment if the risk of bleeding is well controlled, in association with anti-IL6 and corticosteroids.